The Utility of a Protection Motivation Theory Framework for Understanding Sedentary Behavior

Multilevel determinants of sedentary behavior (SB), including constructs couched within evidence-based psychological frameworks, can contribute to more efficacious interventions designed to decrease sitting time. This study aimed to: (1) examine the factor structure and composition of sedentary-derived protection motivation theory (PMT) constructs and (2) determine the utility of these constructs in predicting general and leisure sedentary goal intention (GI), implementation intention (II), and self-reported SB. Sedentary-derived PMT (perceived severity, PS; perceived vulnerability, PV; response efficacy, RE; self-efficacy, SE), GI, and II constructs, and a modified SB questionnaire were completed by undergraduate students (n = 596). SE was broken into three psychological (productive, focused, tired), and two situational (studying, leisure) constructs to capture the main barriers to reducing sitting time. After completing socio-demographics and the PMT items, participants were randomized to complete general or leisure GI and II. Based on model assignment, they completed either the general or leisure SB questionnaire one week later. Irrespective of model, exploratory followed by confirmatory factor analysis revealed that the PMT items grouped into eight coherent and interpretable factors consistent with the theory\u27s threat and coping appraisal tenets: PV, PS, RE, and five scheduling SE constructs (tired, productive/focused, TV/video games/computer, studying at home, studying in library/Wi-Fi area). Using linear regression, general and leisure models predicted 5% and 1% of the variance in GI, 10% and 16% of the variance in II, and 3% and 1% of the variance in SB, respectively. Variables that made unique and significant contributions were: RE (general) and SE (leisure) for goal intention; PV and RE (general), PV, RE, and SE (leisure) for implementation intention; and only goal intention (leisure) for SB. Support now exists for the tenability of an eight-factor PMT sedentary model and its utility in predicting II and to a lesser extent GI and behavior

A randomized, controlled trial of initial anti-retroviral therapy with abacavir/lamivudine/zidovudine twice-daily compared to atazanavir once-daily with lamivudine/zidovudine twice-daily in HIV-infected patients over 48 weeks (ESS100327, the ACTION Study)

<p>Abstract</p> <p>Background</p> <p>Traditional first line regimens containing a non-nucleoside reverse transcriptase inhibitor or protease inhibitor may not be suitable for a subset of antiretroviral-naïve patients such as those with certain co-morbidities, women of child-bearing potential, and intolerability to components of standard first line therapy. This study was conducted to determine if alternate treatment options may meet the needs of both general and special patient populations. The ACTION study was a randomized, open-label, multicenter, 48-week trial that compared the safety and efficacy of a triple nucleoside regimen versus a protease inhibitor plus a dual nucleoside regimen in HIV-1 treatment-naïve subjects.</p> <p>Results</p> <p>279 HIV-infected subjects with HIV-1 RNA (VL) >5000 but < 200,000 copies/mL (c/mL) and CD4+ count ≥ 100 cells/mm³were randomized (1:1) to receive abacavir sulfate/lamivudine/zidovudine (ABC/3TC/ZDV) twice-daily or atazanavir (ATV) once-daily plus lamivudine/zidovudine (3TC/ZDV) twice-daily. Protocol-defined virologic failure was based on multiple failure criteria.</p> <p>Non-inferiority of ABC/3TC/ZDV to ATV+3TC/ZDV was established with 62% vs. 59% of subjects achieving a VL < 50 c/mL at week 48, [ITT(E), M/S = F, 95% CI: -5.9, 10.4]. Similar results were observed in the 230 (82%) subjects with baseline VL<100,000 c/mL (ABC/3TC/ZDV vs. ATV+3TC/ZDV), 66% vs. 59%; 95% CI: -5.6, 19.5. However, ABC/3TC/ZDV did not meet the non-inferiority criterion compared to ATV+3TC/ZDV in the 48 subjects with baseline VL ≥ 100,000 c/mL, 39% vs. 60%; 95% CI: -49.2, 7.4, respectively. Protocol-defined virologic failure was similar between groups.</p> <p>Conclusion</p> <p>ABC/3TC/ZDV demonstrated comparable virologic efficacy to ATV+3TC/ZDV in this population over 48 weeks. In those with a baseline VL ≥ 100,000 c/mL, subjects in the ATV+3TC/ZDV showed better virologic efficacy. Both regimens offer benefits in select therapy-naïve subjects.</p> <p>Trial Registration</p> <p>[Clinical Trials Identifier, NCT00082394].</p

Making a ‘sex-difference fact’:Ambien dosing at the interface of policy, regulation, women’s health, and biology

The U.S. Food and Drug Administration’s (FDA) 2013 decision to lower recommended Ambien dosing for women has been widely cited as a hallmark example of the importance of sex differences in biomedicine. Using regulatory documents, scientific publications, and media coverage, this article analyzes the making of this highly influential and mobile ‘sex-difference fact’. As we show, the FDA’s decision was a contingent outcome of the drug approval process. Attending to how a contested sex-difference fact came to anchor elite women’s health advocacy, this article excavates the role of regulatory processes, advocacy groups, and the media in producing perceptions of scientific agreement while foreclosing ongoing debate, ultimately enabling the stabilization of a binary, biological sex-difference fact and the distancing of this fact from its conditions of construction

Experience and expectations of patients on weight loss: The Learning Health System Network Experience

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152010/1/osp4364_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152010/2/osp4364.pd

Timing of Moderate Level Prenatal Alcohol Exposure Influences Gene Expression of Sensory Processing Behavior in Rhesus Monkeys

Sensory processing disorder, characterized by over- or under-responsivity to non-noxious environmental stimuli, is a common but poorly understood disorder. We examined the role of prenatal alcohol exposure, serotonin transporter gene polymorphic region variation (rh5-HTTLPR), and striatal dopamine (DA) function on behavioral measures of sensory responsivity to repeated non-noxious sensory stimuli in macaque monkeys. Results indicated that early gestation alcohol exposure induced behavioral under-responsivity to environmental stimuli in monkeys carrying the short (s) rh5-HTTLPR allele compared to both early-exposed monkeys homozygous for the long (l) allele and monkeys from middle-to-late exposed pregnancies and controls, regardless of genotype. Moreover, prenatal timing of alcohol exposure altered the relationship between sensory scores and DA D2R availability. In early-exposed monkeys, a positive relationship was shown between sensory scores and DA D2R availability, with low or blunted DA function associated with under-responsive sensory function. The opposite pattern was found for the middle-to-late gestation alcohol-exposed group. These findings raise questions about how the timing of prenatal perturbation and genotype contributes to effects on neural processing and possibly alters neural connections

Methodological standards in non-inferiority AIDS trials: moving from adherence to compliance

BACKGROUND: The interpretation of the results of active-control trials regarding the efficacy and safety of a new drug is important for drug registration and following clinical use. It has been suggested that non-inferiority and equivalence studies are not reported with the same quantitative rigor as superiority studies. METHODS: Standard methodological criteria for non-inferiority and equivalence trials including design, analysis and interpretation issues were applied to 18 recently conducted large non-inferiority (15) and equivalence (3) randomized trials in the field of AIDS antiretroviral therapy. We used the continuity-corrected non-inferiority chi-square to test 95% confidence interval treatment difference against the predefined non-inferiority margin. RESULTS: The pre-specified non-inferiority margin ranged from 10% to 15%. Only 4 studies provided justification for their choice. 39% of the studies (7/18) reported only intent-to-treat (ITT) analysis for the primary endpoint. When on-treatment (OT) and ITT statistical analyses were provided, ITT was favoured over OT for results interpretation for all but one study, inappropriately in this statistical context. All but two of the studies concluded there was "similar" efficacy of the experimental group. However, 9/18 had inconclusive results for non-inferiority. CONCLUSION: Conclusions about non-inferiority should be drawn on the basis of the confidence interval analysis of an appropriate primary endpoint, using the predefined criteria for non-inferiority, in both OT and ITT, in compliance with the non-inferiority and equivalence CONSORT statement. We suggest that the use of the non-inferiority chi-square test may provide additional useful information

NetDiff – Bayesian model selection for differential gene regulatory network inference

Differential networks allow us to better understand the changes in cellular processes that are exhibited in conditions of interest, identifying variations in gene regulation or protein interaction between, for example, cases and controls, or in response to external stimuli. Here we present a novel methodology for the inference of differential gene regulatory networks from gene expression microarray data. Specifically we apply a Bayesian model selection approach to compare models of conserved and varying network structure, and use Gaussian graphical models to represent the network structures. We apply a variational inference approach to the learning of Gaussian graphical models of gene regulatory networks, that enables us to perform Bayesian model selection that is significantly more computationally efficient than Markov Chain Monte Carlo approaches. Our method is demonstrated to be more robust than independent analysis of data from multiple conditions when applied to synthetic network data, generating fewer false positive predictions of differential edges. We demonstrate the utility of our approach on real world gene expression microarray data by applying it to existing data from amyotrophic lateral sclerosis cases with and without mutations in C9orf72, and controls, where we are able to identify differential network interactions for further investigation